HUT71727A - Composition for combating ageing of the skin, acting simultaneously on the surface layers and deep layers of the skin, and use thereof - Google Patents

Abstract

The composition of the invention comprises a first dispersion of lipid vesicles capable of penetrating the deep skin layers and containing at least one active agent chosen from hydrating, anti-free-radical and keratolytic agents, proteins, enzymes, antielastase and anticollagenase agents and fatty acid derivatives for treating these deep layers, and a second dispersion of lipid vesicles capable of penetrating the superficial skin layers and containing at least one active agent chosen from keratolytic, firming, hydrating, surface restructuring and anti-free-radical agents for treating these superficial layers.

Description

Concurrent skin and deep skin anti-aging treatment and application L'OREAL, Paris, France

inventors:

RIBIER Alain, Paris SIMONNET Jean-Thierry, Paris GIRERD Florence, Paris GAGNABIEN-CABANNE Francoise, Chatillon France

Date of filing: 29.12.1994.

Priority: 12/30/1993 (93-15867)

France

80807-8280-SZŐ / KmO • · · · * ··· · «·, ..,. · _ _Β ...........

'......

BACKGROUND OF THE INVENTION This invention relates to cosmetic or dermatological treatment of skin defects and disorders, including scalp. More particularly, the present invention relates to a composition for combating skin aging, comprising at least one active ingredient containing at least two lipid vesicles of different categories.

The present invention also relates to the use of this composition for combating skin aging and to a treatment method for combating skin aging.

There are many examples of cosmetic or dermatological preparations for the treatment of the skin which contain one or more active ingredients for the treatment of the skin, which are encapsulated in lipid spherules (lipid spheres) or lipid vesicles (lipid vesicles). ). Lipid spherules and vesicles are also called liposomes.

By lipid spherules and vesicles is meant particles formed by one or more membranes containing concentric lamellae, which comprise one or more bimolecular layers of amphiphilic lipids encapsulating an aqueous phase. The aqueous phase contains water-soluble drugs, while the bimolecular layers of amphiphilic lipids may contain lipophilic drugs.

The average diameter of such spherules is generally between 10 nm and 5000 nm.

There are 2 408 387 mentioned in the certificates of addition of a number of French, we published a communication on this matter, * • · · · · · · · · * _β ···· ·· ·· · - '* · · · * * * ς. Which describes a formulation based on aqueous dispersions of at least one active ingredient in an encapsulated, ionic or non-ionic lipid spherule. Specifically, this document discloses compositions comprising at least two dispersions of spherules containing different active ingredients to form a mixed system, i.e., a system in which the first dispersion of spherules containing a first active ingredient is combined with a second dispersion of a second category containing active spherules. makes possible the simultaneous action of the two categories of active substances at the time of treatment and possibly the achievement of a synergistic effect which would not be achieved if the two categories of active substances act in succession individually.

Cosmetic and / or dermatological compositions have been developed to combat the aging of the skin (anti-aging skin), which allow the simultaneous action of two different active ingredients, as well as the action of these active ingredients on different areas of the skin, i.e., superficial and deep layers. As a result, the efficacy of these formulations as well as the complementary and synergistic effects of the anti-aging (anti-aging) agents used are greatly enhanced.

In addition, we have developed cosmetic or dermatological anti-aging formulations that allow the same active ingredient to act simultaneously on the surface and deep layers of the skin. This allows a more complete and therefore more effective treatment of the skin disorder.

• · · ·

The composition of the present invention is also useful in combating the appearance of aging, in removing signs of age, such as wrinkles, and in protecting the skin from light radiation.

It is known that during the course of aging various signs appear which are very characteristic of skin aging and are mainly reflected in the modification of the structure and function of the skin. This aging process is physiological, but it is also triggered by light effects; that is, it is attributable to the repeated exposure to the skin, which results in the formation of oxygenated free radicals acting on the skin components.

The main clinical signs of skin aging are, in particular, the appearance of deep wrinkles that multiply with age. In particular, disintegration of the skin particles is observed, resulting in a less even and anisotropic microstructure renewal.

In addition, the complexion usually changes color, becoming pale and yellowish, which is probably due mainly to a deterioration of microcirculation (less hemoglobin in the capillaries of the skin). Many discolored patches appear on the skin surface due to damaged melanogenesis (melanin formation). There are scattered areas of the skin, sometimes hair follicles.

A further clinical sign of aging is the dry and crude appearance of the skin, which is essentially the result of a more prominent exfoliation: the scattered rays of light also contribute to the slightly greyish complexion.

··· · · · · ··· * · «··« ··· ·

Finally, a decrease in the elasticity and firmness of the skin is observed, which, as in the case of wrinkles, is due at least in part to atrophy of the skin and epidermis and to the flattening of the structure of the skin.

Thus, it is observed that the clinical signs of skin aging are mainly due to the loss of function of the main biological mechanisms involved in the skin.

The compositions of the present invention are capable of treating already formed wrinkles, preventing skin aging, and protecting the skin by inhibiting the formation of free radicals.

It is well known that the skin consists of surface layers, stratum corneum and deep layers, living epidermis and dermis. The specific delivery of an active ingredient to the surface layers of the skin and the simultaneous delivery of the same or another active ingredient to the deep layers of the skin have not been known.

The present invention relates to an anti-aging composition which acts simultaneously on the surface layers and the deep layers of the skin. This composition is characterized by the fact that a first dispersion of lipid vesicles which penetrate into the deep layers of the skin and which contain at least one active ingredient, a moisturizing agent, free radical active agents, keratolytic (corneal solubilizing) agents, protids, enzymes, anti-elastase and anti-collagenase containing active substances as well as fatty acid derivatives for the treatment of these deep layers - and a second dispersion of lipid vesicles capable of penetrating the surface layers of the skin and having at least one active ingredient; - • ··· · *.,. · ,, _{> φ} · ···· ··· ♦ ·

They contain 6 substances as keratolytic agents, firming agents, moisturizers, surface-restoring agents and anti-free radicals for treating these surface layers.

In a particular embodiment of the invention, the active agent pouch (s) in the first and second dispersions of vesicles are the same. "

A method has been used to classify vesicles which allows one of ordinary skill in the art to readily select lipid vesicles capable of delivering the active ingredient to the deep layers of the skin: these are known as deep vesicles; and the selection of lipid vesicles capable of delivering the active ingredient to the surface layers of the skin, known as surface active vesicles.

This classification is based on the diffusion constant D of a probe introduced into vesicles. This probe is ASL [Chemically N-oxy-Z.Z.e.-tetramethyl] -piperidyl] -N.N-dimethyl-N- (hydroxyethyl) ammonium iodide (I).

Vesicles having a D constant of the probe diffusion to the stratum corneum greater than ¹ x 10 ⁷ cm ² s' ¹ are capable of penetrating deep layers of the skin.

Vesicles having a D constant of the probe diffusion to the stratum corneum of less than ¹ x 10 ⁷ cm ² s' ¹ are capable of delivering the active ingredient to the skin surface layers.

The first category of vesicles, the so-called "deep-action vesicles", are generally in a liquid state at room temperature (about <RTI ID = 0.0> C) </RTI>; while the second category of vesicles, so called surface active vesicles, are generally gel-like at room temperature. The method of understanding the state of the vesicles consists in determining the transition temperature of the main lipid from the main lipid forming the membrane of the vesicle to the lamellar gel state by differential thermal analysis (DTA).

Other parameters of these vesicles are related to their ability to deliver the active ingredient to a greater or lesser depth of the skin. This is especially true for the degree of encapsulation.

Glucose is a commonly used marker for this type of determination. See, in more detail, Liposomes: A Practical Approach, R.R. C. New IRL Press 125-136. p. (1990)].

The degree of encapsulation (encapsulation) is expressed in μΙ of the volume of glucose solution encapsulated in the vesicles relative to the mg mg of lipid-forming lipids. The extent of encapsulation was determined at 24 hours (4h time _T2) immediately after the separation step of free glucose and glucose encapsulated (T _o time) and after this separation step.

The difference between two such consecutive determinations shows the permeability of vesicles to encapsulated glucose; this can also be referred to as encapsulation potential.

Encapsulation potential of first category vesicles (which deliver the active ingredient to the deep layers of the skin) · ··· · · · ···

- 8 high against small, water-soluble molecules, preferably modeled on glucose; this encapsulation potential is maintained for at least 24 hours. The second category of vesicles (which deliver the active ingredient to the surface layers of the skin) does not retain glucose in the encapsulated state for the same amount of time.

The major lipids constituting vesicles of the first category (which release the active ingredient deeply) are composed of at least one linear, saturated aliphatic chain of 16 to 30 carbon atoms; such as hydrogenated phospholipids (vegetable or egg derived), saturated synthetic phospholipids, such as dipalmitoyl phosphatidylcholine, and polyolalkyl ethers or polyolalkyl esters containing one or two aliphatic chains per molecule. These lipids can be used alone or as mixtures.

The main lipids constituting the second category of vesicles (which deliver the active ingredient to the surface) are mainly selected from the group consisting of ionic lipids, in particular phospholipids of C 16 -C 30 unsaturated aliphatic chains of vegetable or egg origin; and nonionic lipids, such as polyolalkyl ethers or polyolalkyl esters containing one or more aliphatic chains per molecule, including at least one aliphatic chain having less than 16 carbon atoms, such as lauryl 1-pol to liceryl-6-cetararyl glycol ether. The latter material is described in detail in French patent application FR 92-09603 filed by L'Oréal.

It is known to incorporate at least one excipient into the lipid phase forming the lipid membrane of vesicles. This · ♦ ♦ ♦ ** ** ** ** ** ** ** ** ** ** · **

- 9 substances selected from: sterols [phytosterols, cholesterol or polyoxyethylated phytosterols]; long-chain alcohols, diols and triols (e.g., phytantriol); long-chain amines and their quaternary ammonium derivatives; phosphoric acid esters of fatty alcohols and their alkali metal salts (sodium or potassium salts), such as dicetyl phosphate, sodium dicetyl phosphate; alkali metal salts of alkyl sulfates (sodium cetyl sulfate), cholesterol sulfate, or cholesterol phosphate; phosphatidic acid sodium salt; and lipoamino acids and their salts, such as sodium acyl glutamates.

Examples of Category 1 vesicles (which deliver the active ingredient to the deep layers of the skin) include vesicles derived from the following lipids (CTFA names):

- A / cholesterol / casein-lipoamino acid, in particular 45/45/10 by weight (where A is triglyceryl cetyl ether marketed by Chimex as Chimexane NL);

- B / cholesterol / dicetylphosphate, in particular 60/35/5 by weight (where B is a mixture of triglyceryl mono-, di- and tricetyl ethers marketed by Chimex under the name Chimexane NT),

- Span 40 (product of ICI; or sorbitan palmitate) / cholesterol / sodium acylglutamate (marketed by Ajinomoto as HS11), in particular 47.5 / 47.5 / 5 by weight;

- PEG 8-stearate / cholesterol / sodium acylglutamate, in particular 47.5 / 47.5 / 5 by weight (where PEG 8-stearate is polyethylene containing 8 ethylene oxide units) ^{«·: ···:} ··· * '' · stearate, PEG 400 stearate, which brings the circulation Unichema under the tradename);

- PEG 8-stearate / cholesterol / phytantriol / sodium acylglutamate, in particular 47.5 / 20 / 27.5 / 5 by weight;

hydrogenated lecithin / polyoxyethylenated phytosterol containing a 5-ethylene oxide unit, in particular 60/40 by weight;

- polyoxyethylated methyl glucose distearate containing 20 units of ethylene oxide / cholesterol / sodium acyl glutamate, in particular 45/45/10 by weight (distearate is e.g. Glucam E 20 distearate from Amerchol) commercial product);

- cholesterol / dicetyl phosphate, in particular 47.5 / 47.5 / 5 by weight;

diglyceryl distearate (e.g. Nihon commercial product Emalex DS G2) / cholesterol / sodium acyl glutamate, 45/45/10;

sucrose mono- and distearate (e.g., Groten product PSE 141 G from Grillo) / cholesterol / sodium acyl glutamate, in particular 45/45/10; and tetraglyceryl distearate (e.g. Tetraglyn 3S from Nikkol) / cholesterol / sodium acyl glutamate, in particular 45/45/10 by weight.

Examples of the second category of vesicles (which deliver the active ingredient to the surface layers of the skin) are vesicles prepared from the following lipids:

- sunflower lecithin,

- Natipide II (soybean lecithin / ethanol / water 60/20/20 by weight, product of Nattermann),

- C (40/30/30 by weight mixture of soya lecithin / cholesterol / propylene glycol marketed by Nattermann as NAT 50 PG); as well as

D / dimyristyl phosphate, in particular 95/5 by weight (wherein D is lauryl polyglyceryl-6-cetaryl glycol ether, marketed by Chimex as Chimexane NS).

Table I below shows the value of the diffusion constant D for the ASL corneal layer and the D diffusion constant D for the epidermis / skin layers for some vesicles prepared using the above lipids; and the degree of encapsulation of glucose and the phase transition temperature of the main lipid that makes up the membrane. The diffusion constant was measured at an encapsulated ASL concentration of 0.35% by weight based on the total weight of the formulation.

. spreadsheet

Phase transition temperature ° C 09 54 50 55 Rate of glucose encapsulation in μΙ / mg 3 00 (D £ I 13.8 7.5 11.1 13.8 14.4 Diffusion coefficient D in 10 ' ⁷ cm ² s' ¹ Epidermis / irhá- in tendon (XI (XI (XI stratum corneum 42 58 42 42 proportions crowd% ________ UNS) ________ 45/45/10 (67.5 / 67.5 / 15) 60/35/5 (90 / 52.5 / 7.5) 47.5 / 47.5 / 5 (71.25 / 71.25 / 7.5) 47.5 / 47.5 / 5 (71.25 / 71.25 / 7.5) lipid system Category 1 = Deep effect A / cholesterol / casein -lipoaminosav B / cholesterol / dicetyl phosphate Span 40 / Cholesterol / Sodium acyl qlutamát PEG 8-stearate / cholesterol / sodium acyl glutamate reference song IXI CO

CO «

«···

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* · ·· **

»· ··· ♦

Phase transition temperature ° C 55 80 SHE V She V <0 1 '(0 She co y Φ -C J? 22 the co M She She She apse in g 1- . SHE She <0 M 00 E N {8 - <o c > to 1- ·> ·· • • 4 · CO She V 0 «ά £ co c U) CM CM £ ^C E CB CM - Φ (D '<8 -Q cm She SHE She Ο X » JZ itv ¹ Φ Φ CO u. S ^W F λ c co θ O ^ r Ν θ conditions - □ * £ Q φ φ co CO co M · 25 Q u. □ 00 She SHE She L. to N (0 lf> SHE? ΪΛ M CD She She She She She <0 O> CM co > »C S cn Φ E * S £ i She 19/01 100 150 CD / 24 / / 20 / o co < :SHE * + (0 m 20 30 09 o cn V " <0 c * <Σ oxy the lake '<0 CB JC '(0 c Luta / Poly ( zterir there h ITIN ol / water Ethereal- · .- o JKÍ ystem depth 1 CO 0 L- Φ N ω Φ -acyl-g lecithin t) fit - of him RGO-lec handle II n / ETAM lecithin / s: σ> c Φ V. D II NEW She E <D She φ Q. Q. 'She CB Q_ 3 Φ N CO M— CQ u. CL CB u ro u. □ Shoot tri N Φ Φ C u. Ό z Φ (soy the CD u. 'CB C 'Φ σ CB z <8 Φ CB CB Φ c G <D Ό κι Φ c + - »N She o λ- Φ 1 C0 CO She V co L. Ό X CM 11 I SHOOT co rí CO cn I Jz

• · · ·

Phase transition temperature ° C Rate of glucose encapsulation in μΙ / mg She o Csf Diffusion coefficient D in 10 ' ⁷ cm ² s' ¹ Epidermis / irhá- in 0.2 stratum corneum 0.3 proportions crowd% ________ IMS) ________ 95/5 (142.5 / 7.5) lipid system Category 1 = Deep effect D / dimyristyl phosphate reference song 10th

• ·

The diffusion constant D is measured by a combination of two methods: first, the ASL paramagnetic probe, one-dimensional and periodic electron paramagnetic resonance (EPR); on the other hand, performing EPR kinetic imaging. A description of these two methods can be found in V. Gabrijelcic et al., Evaluation of Liposomes as Drug Delivery Carriers by One-Dimensional EPR Imaging (International J. of Pharmaceutics 62: 75-79 (1990)); and V. Gabrijelcic et al., Measurement of Skin Penetration of Liposome-Encapsulated Molecules by Kinetic Mapping of Nitroxide Reduction (Periodicum Biologorum 93, 245-246 (1991)).

The extent of encapsulation is measured as described in R.R.C. New documentary; the phase transition temperature is also determined as described therein.

It is preferable to use more than one active ingredient in both categories of vesicles at the same time, if the same function and / or effect on the skin and / or the deeper layers of these vesicles produce the same type of effect; Thus, the surfactant and the depth-acting agents are complementary (complementary).

Depth and surface active agents used in the present invention are commonly used in the field of cosmetics or dermatology.

Depth active agents are selected from hydrating agents, free radical agents, keratolytic agents, protides, fatty acid derivatives, enzymes, anti-elastase agents and anti-collagenase agents.

··· »

Examples of moisturizers include sodium lactate, polyols, and in particular glycerol, mannitol, and amino acids.

Examples of free radical scavengers are phosphonic acid derivatives, ethylenediaminetetraacetic acid and its salts such as sodium salt, guanosine superoxide dismutase, tocopherol (vitamin E) and its derivatives (e.g. acetate); ethoxyquin, lactoferrin, lactoperoxidase, and nitroxide derivatives.

Examples of deep-acting keratolytic agents include fruit-derived α-hydroxy acids such as glycolic acid, lactic acid, citric acid, mandelic acid, and mixtures thereof; and salicylic acid derivatives such as 5- (n-octanoyl) salicylic acid or 5- (n-dodecanoyl) salicylic acid; and retinol (vitamin A) and its derivatives.

Examples of protids include peptide derivatives and proteins (wheat or soy derived products) and their hydrolysates. Exemplary fatty acid derivatives include polyunsaturated phospholipids, including polyphenolic essential fatty acid phospholipids.

Examples of anti-elastase agents include peptides derived from legume seeds, such as those marketed by Laboratories Serobiologiques (Nancy) as Parelastyl. Among collagenase agents, metalloprotease inhibitors such as ethylenediaminetetraacetic acid (EDTA) and cysteine are noteworthy.

Enzymes that can be used as deep-acting substances are especially DNA repair enzymes.

· · · *

Surfactants are selected from the group consisting of keratolytic agents, firming agents, moisturizers, surface-restoring agents, and free radical scavengers.

Among the surface-active keratolytic agents are α-hydroxy acids, such as lactic acid, salicylic acid and 5- (n-octanoyl) salicylic acid.

Among the firming agents are protein hydrolysates (e.g., soy protein derived hydrolysates), such as the product marketed by Silab as Tensine.

Peptide extracts from soy or collagen, such as the product Noptigone II from Coletica, may be mentioned as surface-repair agents.

Surfactant moisturizers may be used which are the same as those mentioned for the deep-acting active ingredients.

Free radicals include tocopherol (vitamin E) and its derivatives (acetate), superoxide dismutases, ethoxyquin, guanosine, lactoperoxidase, glutathione peroxidase, as well as free radical plant extracts such as the aqueous extract of wheat germ Detox market.

Surfactants and depth-active agents may be present in an amount of 0.02 to 10% by weight of the total composition. Further, both categories of vesicles may contain other cosmetic agents, such as trace elements, sugars.

The compositions of the present invention can be formulated into any dosage form that is generally applied topically, such as aqueous gels, emulsions, lotions, ointments, serums, particularly oily droplets dispersed by vesicles, such as those described in FR-A-2 405 921; FR-A-2 490 504.

As is known in the French patents cited above, in addition to the vesicles, the compositions of the present invention include vegetable, mineral, silicone or synthetic oils (dispersed in an aqueous phase) and hydrophilic excipients such as gelling agents, preservatives, antioxidants, antioxidants, and lipophilic excipients such as essential oils and fragrances, pigments, fillers. For example, polyethylene rings can be used to achieve a cleaning effect (rubbing). The dispersed oil may be present in an amount of 2 to 40% by weight of the total composition; while the excipients may represent from 0.1 to 10% by weight of the total weight.

A further object of the present invention is the use of a composition as defined above for the manufacture of an anti-aging ointment, and a method of anti-aging comprising applying the composition of the invention to the skin.

Other features and advantages of the invention will be clearly apparent from the following description, which is provided by way of illustration, but without limitation.

···· ····

- 19A) Preparation of lipid vesicles containing ASL

Lipids forming the wall of the vesicles were weighed and dissolved in 10 ml of methanol. The methanolic solution was transferred to a 50 ml round-bottomed flask, fitted with a rotary evaporator and kept at 30 ° C with the aid of a thermostat. The evaporation was continued until dry lipid film was deposited on the flask wall.

The flask was then charged with 3 mL of a 0.01 M aqueous solution of ASL and the mixture was shaken by hand for about 10 minutes. at room temperature (20 ° C), while Table I, Sections 1-6. at 50 ° C. The mixture was allowed to equilibrate at room temperature for 2 hours, then the dispersion was placed in a dialysis bag and contacted with 500 ml of distilled water. Dialysis occurs overnight, the next day the water is changed and dialysis is continued for another 4 hours.

A cotton thread 0.3 mm thick was dipped in the vesicle dispersion and contacted with a skin cut out of a pig's ear, previously obtained from a food supply slaughterhouse.

The ear sample is rinsed with water and cut into slices 1 mm thick, 5 mm wide, 10 mm long, into a treatment cell. Diffusion of ASL toward the skin is measured 24 hours after skin sampling.

-20 B) Preparation of Cosmetic Preparation

1. Preparation of first category vesicles (diffusible in deep layers)

Vesicles (depth effect) are prepared by a method generally used for the co-fusion of various selected membrane components (see Table I). Melt the lowest _(Tm), melting membrane component, added to the other membrane component, as well as active ingredients, and the mixture was homogenized with moderate stirring and is finally partially hydrated, while maintaining the above-defined T _m melting temperature.

To the paste thus obtained is added an aqueous solution of at least one first active ingredient suitable for depth treatment. The mixture was stirred to complete hydration turbine 90 minutes while maintaining the temperature T _m. Subsequently, one or more additional depth treatment agents are added to the reaction mixture, homogenized and the temperature of the mixture is reduced to room temperature (20 ° C).

2. Preparation of second category (surface diffusing) vesicles

An aqueous solution of one or more second active agents for surface treatment is added to the selected mixture of components for forming the membrane of surfactant vesicles (see Table I) at room temperature (20 ° C) with simple mixing. Thus, surface-active vesicles encapsulating the second surfactant are encapsulated.

3. Preparation of a double liposome-type composition

The fatty phase of the preparation (oils) is added to the medium containing the deep-acting vesicles and dispersed at room temperature with stirring. The resulting reaction mixture is admixed with a mixture of surface active vesicles and optionally adjuvants such as preservatives, gelling agents which can be neutralized with a base such as triethanolamine or sodium hydroxide, if necessary, and perfumes may be added.

The product thus obtained is a soft, uniform, white cream which can be applied in the cosmetic and / or dermatological field depending on the nature of the active ingredient (surface and depth of action) chosen.

Representative examples of cosmetic compositions of the present invention are described below.

Example 1

Anti-Wrinkle Double Liposome Cream

- Preparation A: Components of deep-acting liposomes:

PEG 8-stearate / cholesterol / sodium acylglutamate 47.5 / 47.5 / 5 by weight 11.26g

Tocopherol acetate 1.00g

Glycerin 5.63g

Soy Protein Hydrolyzate (active ingredient) 0.37g

Ethylenediaminetetraacetic acid disodium salt (complexing agent) 0.19g

Mineralized water as needed

100 g

- Preparation B: components of liposomes with surface effect:

Natipide II (Product by Natterman) 33.33 g Glycerin (active ingredient) Natural collagen of marine origin 33.33 g (Drug) Mineralized water as needed - Components of a dual liposome preparation: 8.33 g 100 g The preparation 26.65 g Preparation B 9.00 g Vegetable oil 16.40 g volatile silicone oil 4.00 g Retinyl palm drink 0.60 g lllatanyag 0.40 g Citric acid 0.02 g

It consists of a copolymer of vinylidene chloride

microspheres 0.20 g preservatives 1.18g Carboxyvinyl polymer (gelling agent) 0.50 g Sodium hydroxide 0.15 g Mineralized water as needed 100 g

Example 2

Free radical double liposome type cream

- Preparation A: Components of deep-acting liposomes:

PEG-8 stearate / cholesterol / sodium acyl-

-glutamate in a weight ratio of 47.5 / 47.5 / 5 10.33 g a-Tocopherol 1.00g Glycerol 13.77 g

- 23 Guanosine 0.30 g

Ethylenediaminetetraacetic acid, disodium salt

(Drug) Mineralized water as needed 0.17 g 100 g

Preparation B: components of surface active liposomes:

Natipide II (product of Nattermann) Wheat germ extract (active ingredient) (Silab 35.29 g (marketed as Detoxiline) 5.88 g Glycerol 35.30 g Mineralized water as needed - Components of a dual liposome preparation: 100 g The preparation 29.05 g Preparation B 8.50 g Vegetable oil 20.50 g Volatile silicone oil 3.50 g lllatanyagok 0.40 g Citric acid 0.02 g preservatives 1.18g Carboxyvinyl polymer (gelling agent) 0.50 g Sodium hydroxide 0.15 g Mineralized water as needed 100 g

Example 3

Anti-aging dual liposome type cream

- Preparation A: Components of deep-acting liposomes:

PEG 8-stearate / cholesterol / sodium acyl- 11.52g

-glutamate in a weight ratio of 47.5 / 47.5 / 5

Glycerol

5.76 g

• · • * · ·

Ethylenediaminetetraacetic acid, disodium salt 0.19 g (chelating agent) Mixture of alpha-hydroxy acids derived from fruits (35/15/8 by weight of lactic acid / glycolic acid / citric acid- rabbit mix) 1.92 g Mineralized water as needed 100 g - Preparation B: components of liposomes with surface effect: Natipide II (product of Nattermann) 35.29 g Lactic acid (active ingredient) 5.00 g Mineralized water as needed 100 g - Components of a dual liposome preparation: The preparation 26.05 g Preparation B 8.50 g Vegetable oil 17.00 g Volatile silicone oil 4.00 g lllatanyagok 0.40 g preservatives 1.18 g Carboxyvinyl polymer (gelling agent) 0.50 g Sodium hydroxide 0.15 g Mineralized water as needed 100 g

Example 4

Anti-aging dual liposome type cream

- Preparation A: Components of deep-acting liposomes:

PEG 8-stearate / cholesterol / sodium acyl

-glutamate in a weight ratio of 47.5 / 47.5 / 5

Tocopherol acetate

5- (n-Octanoyl) salicylic acid (active ingredient)

11.26 g

0.37 g

0.37 g

-25 Glycerin 5.63 g

Ethylenediaminetetraacetic acid disodium salt 0.19 g

Mineralized water as needed for 100 g

- Preparation B: components of liposomes with surface effect:

Natipide II (product of Nattermann) 36.58g

Salicylic acid (active ingredient) 2.44g

Glycerin 36.60g

Mineralized water as needed for 100 g

- Components of a dual liposome preparation:

The preparation was 26.65g

Preparation B 8.20g

Vegetable oil 17.00g

Volatile silicone oil 4.00g lilac 0.40g

Citric acid 0.02g

Preservatives 1.70g

Carboxyvinyl polymer (gelling agent) 0.50g

Sodium hydroxide 0.15 g

Mineralized water as needed

100 g

Claims (17)

Patent claims 1. An anti-aging, simultaneous action on skin surface layers and deep layers, comprising a first dispersion of lipid vesicles - capable of penetrating the deep layers of the skin and containing at least one active ingredient as a moisturizer, antifungal agents, keratolytic agents. , protids, anti-elastase and anti-collagenase agents, enzymes and fatty acid derivatives for the treatment of these deep layers - and a second dispersion of lipid vesicles capable of penetrating the surface layers of the skin, which contain at least one active ingredient, keratolytic agents, firming agents, , surface-restoring agents and anti-free-radical agents for treating these surface layers. The composition of claim 1, wherein the vesicles in the first dispersion are ASL [chemically N- (1-oxyl-2,2,6,6-tetramethyl-4-piperidyl) -N, N-dimethyl-N- ( hydroxyethylammonium iodide] diffuses towards the stratum corneum (corneal layer) with a value greater than 1.10 'to ⁷ cm ² s' ¹ , while vesicles in the second dispersion provide 1.10' to the stratum corneum of the ASL. ⁷ cm ² less than ¹ '. The composition of claim 1 or 2, wherein the vesicles of the first dispersion are liquid at room temperature and the vesicles of the second dispersion are gel at room temperature. 4. A composition according to any one of claims 1 to 4, wherein the vesicles of the first dispersion provide for the encapsulation of glucose for at least 24 hours, and the vesicles of the second dispersion provide for the encapsulation of glucose for less than 24 hours. 5. The composition of any one of claims 1 to 5, wherein the vesicles of the first dispersion are formed from at least one linear saturated lipid of C 16 -C 30 aliphatic chains. 6. The composition according to any one of claims 1 to 6, wherein the vesicles of the first dispersion are hydrogenated phospholipids of natural origin, saturated synthetic phospholipids, at least one linear aliphatic polyolalkyl ether, or at least one aliphatic polyolalkyl ester or mixtures of at least one lipid. 7. The composition according to any one of claims 1 to 6, wherein the vesicles of the first dispersion are (triglyceryl cetyl ether / cholesterol / casein lipoamino acid), [(a mixture of triglyceryl mono-, di- and tricetyl ether) / cholesterol / dicetyl phosphate], (triglyceryl) acetyl ether / cholesterol / dicetyl phosphate) (sorbitan palmitate / cholesterol / sodium acyl glutamate), (PEG 8-stearate / cholesterol / sodium acyl glutamate), (diglyceryl distearate / cholesterol) acyl glutamate), «·« · - 28 (sucrose mono- and distearate) / cholesterol / sodium acylglutamate, (PEG 8-stearate / cholesterol / phytantriol / sodium acylglutamate), (polyoxyethylated) methyl glucose distearate, containing at least 20 moles of ethylene oxide unit (cholesterol / sodium acylglutamate), (hydrogenated lecithin / (polyoxyethylenated phytosterol), or (tetraglyceryl tristearate / cholesterol / sodium acyl glutamate), at least are formed from a lipid. 8. A composition according to any one of claims 1 to 6, wherein the vesicles of the second dispersion are polyolalkyl-alkyl unsaturated C 16 -C 30 aliphatic chains of naturally occurring ionic phospholipids containing one or more aliphatic chains per molecule, including at least one aliphatic chain of less than 16 carbon atoms. formed from ethers or polyol alkyl esters or mixtures thereof, such as lipids. 9. The composition according to any one of claims 1 to 6, wherein the vesicles of the second dispersion are sunflower lecithin, soya lecithin / ethanol / water, soya lecithin / cholesterol / propylene glycol or lauri l-pol igliceri l-6-ceto-aryl l-glycol lauryl l-ether / dim. selected from at least one lipid selected from the group consisting of iris I-phosphate. 10. A composition according to any one of claims 1 to 6, wherein the active ingredient and the second dispersion have the same function (s) and / or mode of action of the second dispersion. 11. The composition according to any one of claims 1 to 4, wherein the first and second dispersions of the active ingredient (s) are the same. 12. The composition according to any one of claims 1 to 6, wherein the first dispersion is glycerol, phosphonic acid derivatives, ethylenediaminetetraacetic acid and its salts, α-hydroxy acids and their salts, salicylic acid derivatives, peptide derivatives, protein hydrolysates, polyunsaturated phospholipids, contains an active ingredient selected from salicylic acid, tocopherol and its derivatives, retinol and its derivatives, superoxide dismutases, guanosine, lactoperoxidase and lactoferrin. 13. The composition according to any one of claims 1 to 6, wherein the second dispersion is salicylic acid and its derivatives, 5- (n-octanoyl) salicylic acid, α-hydroxy acids, protein hydrolysates, collagen derivatives, glycerol, tocopherol and its derivatives, superoxide dismutases, ethoxyquin, guanosine and contains an active ingredient selected from lactoperoxidase. 14. The composition of any one of claims 1 to 4, further comprising an oil phase dispersed in the aqueous phase. 15. The composition of any one of claims 1 to 5, further comprising hydrophilic or lipophilic adjuvants. 16. Use of a composition according to any one of claims 1 to 6 for the manufacture of an ointment for treating aging. · * · · I 17. A method of treating aging, characterized in that the skin is characterized by a method according to claims 1-15. A composition according to any one of claims 1 to 6 is applied.